1. Regulated expression of thyroid hormone receptor genes provides an additional means of controlling the action of thyroid hormone. We cloned an sequenced a 5'flanking region of the rat thyroid hormone receptor alpha gene, which revealed no presence of TATA and CAAT boxes. Using primer extension assays multiple extension products were observed. A minimal region necessary for promoter activity resides within 193 nucleotides upstream from the major start of transcription. Further analyses showed that a strong positive element is in the splicing junction of the untranslated exon/intron. Only in the presence of the hormone and the receptor the promoter activity was inhibited by 50 - 80% 2. Identification of malic enzyme and myelin basic protein thyroid hormone response elements in different promoters allowed us to study thyroid hormone dependent activation of these promoters by the receptor alpha and beta. We have demonstrated that the more efficient thyroid hormone responsiveness of the myelin basic promoter elicited by the receptor beta depends on both the thyroid hormone response element of the myelin basic protein promoter and TATA box sequences. In the case of the malic enzyme promoter, the more efficient thyroid hormone dependent activation by the alpha receptor requires the thyroid hormone response element of the malic enzyme gene and an element within 122 nucleotides upstream from the start of transcription of this gene.